Breast cancer is the most frequent type of cancer in women in Western societies and in the United States has shown an alarming increase in incidence from 87/100,000 to 104/100,00 within the last five years. It is commonly accepted that early diagnosis and treatment of breast cancer results in a more favorable prognosis; however, despite the increased use of mammography and breast self-examination, the mortality from breast cancer has remained constant. In breast cancer peptide growth factors are believed to have a critical role in tumorigenesis. We have identified specific growth factor activities in murine milk which are unique in that they are predictive of mammary tumor development. Partial purification has identified IGF-1 related activity as the major source of growth factor activity with smaller amount of PDGF related and TGF-beta related activity present. We studied 35 women with breast cyst and found that their breast cyst fluid contained growth factor activities which were similar to those found in murine milk. Total mitogenic activity in these breast cyst fluid samples was directly related to a woman's risk of developing breast cancer. The aims of the proposed research are: 1 confirm the levels of a specific set of growth factor activities; IGF-1, PEIGF and TGF-beta activities in breast cyst fluid and 2) correlate, singly or in combination, the levels of IGF-1, PDGF, TGF beta and total mitogenic activity in breast cyst fluid with the assigned risk of developing breast cancer. Breast cyst fluid samples will be obtained from patients in the High Risk Breast Tummor Clinic at the University of Washington and the Swedish Hospital Breast Clinic. In a blinded study, the level of the specific growth factors in the breast cyst fluid will be determined by standard radioassay techniques and total mitogenic activity determined by 3H-thymidine incorporation assay. Patients will be assigned a risk level for developing breast cancer based on factors know to increase risk. Data will be statistically analyzed to determine correlations. The identification of these specific growth factors might provide a much needed early screen ing system for assessing the risk of developing breast cancer in the form of a simple laboratory assay using body fluids as the test material. In addition, the proposed research may lead to the development of an effective test for monitoring treatment and probability of recurrence as well as to promote the development of immunotherapeutic tools.